This project is concerned with investigating factors responsible for the regulation of human hemoglobin synthesis in thalassemia and the hemoglobinopathies. In patients heterozygous for certain hemoglobinopathies the differential rates of synthesis of hemoglobin A and the abnormal hemoglobin are to be investigated utilizing cell free hemoglobin synthesis in a Krebs ascites tumor system stimulated by globin messenger RNA. In the hemoglobinopathy hemoglobin Leiden we have demonstrated a thalassemic-like imbalance in alpha/beta globin synthesis. We hope to investigate this phenomenon utilizing the cell free globin synthesizing system as well as by RNA-DNA hybridization.